COMMENTARY |
The Decline in Invasive Pneumococcal Disease
Abbreviations: IPD, invasive pneumococcal disease • PCV7, 7-valent pneumococcal conjugate vaccine • NVST, nonvaccine serotype • VSG, vaccine serogroup
The decline in invasive pneumococcal disease (IPD) as reported by Kaplan et al1 confirms the strategy of linking capsular polysaccharide (type-specific carbohydrate) to a protein carrier to enhance immunogenicity in the target age group. Reductions were identified in all 8 geographic sites; in white, African American, and Hispanic children; and for bacteremia, meningitis, and pneumonia. However, unlike the Haemophilus influenzae type b conjugate vaccine, which resulted in the virtual elimination of H influenzae type b disease, IPD persists.2
The 7-valent pneumococcal conjugate vaccine (PCV7) was designed to protect against the 7 most frequent disease-causing serogroups of Streptococcus pneumoniae. Kaplan et al observed that in 2002, 37% of the reduced number of documented episodes of IPD was due to nonvaccine serotypes (NVSTs). This represents a dramatic rise in the proportion but not in the number of cases due to NVSTs. In addition, persistent disease due to vaccine serogroups (VSGs) remained. IPD due to serogroups 14 and 23 were reduced >80%; however, disease due to serogroup 19 was reduced only 31%. Can we do better? The observed decline in IPD was achieved although a nationwide shortage of PCV7 existed between December 2001 and May of 2003, resulting in deferral of the booster dose for almost all children and even fewer doses for others.3 Enhanced availability will not reduce disease due to NVST, but the availability of the booster dose could decrease nasopharyngeal carriage of VSGs further over time, likely resulting in greater declines in IPD due to VSGs. A potentially more-valuable strategy would be expanding the number of serotypes in the formulation. Kaplan et al identified serogroups 1, 3, 15, and 22 as the cause of two thirds of nonvaccine cases. Studies of conjugates with up to 11 antigens including serogroups 1 and 3 have demonstrated immunogenicity. Expanded formulations also offer the potential to meet the needs of the world community (eg, South America, Africa, and Oceana), for which the 7 serogroups in the current formulation are responsible for a substantially smaller proportion (50%–70%) of cases of IPD than in North America.4
A decline in both the absolute number and proportion of cases of IPD due to ceftriaxone-resistant pneumococci was also observed. The decline is likely related to the changing distribution of serogroups (as a result of immunization with PCV7) and the overrepresentation of antimicrobial resistance among VSGs. If the serogroups that are most likely to be antimicrobial resistant are reduced in the community and those that are susceptible remain stable or increase in number, the proportion of pneumococci that are resistant will decline. It is likely also that not all communities will achieve an equivalent decrease in antimicrobial resistance. In communities in which the predominant antimicrobial-resistant pneumococcus is serogroup 19, resistance will persist, because PCV7 is least efficacious against this serogroup. Whether the decline in ceftriaxone resistance will reach a nadir at which vancomycin will no longer be necessary as initial therapy for suspected pneumococcal meningitis remains to be determined.
What about pneumococcal disease in the developing world? The World Health Organization reports that 1 million children, mostly young and living in developing countries, die from pneumococcal disease annually.5 This represents twice the World Health Organization estimate of annual deaths in children from human immunodeficiency virus. With a known technology (conjugated polysaccharides) and an infrastructure for successful vaccine-delivery programs such as polio and measles, why is the human immunodeficiency virus in the headlines and pneumococcal disease in the small print? In 2002, the Global Alliance for Vaccines and Immunization launched a new initiative, Accelerated Development and Introduction Plans, which is designed to address the significant challenges involved in making available new vaccines for developing countries. The program has 3 components: establish the value of each vaccine (eg, disease-burden studies), communicate this value, and deliver the promised value by facilitating the procurement and distribution of these vaccines in developing countries. We have the technology to prevent pneumococcal disease in the world’s children; we need the resources and the commitment from both government and industry to achieve that goal.
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FOOTNOTES |
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Received for publication Dec 9, 2003; Accepted Dec 9, 2003.
Address correspondence to Stephen I. Pelton, MD, Section of Pediatric Infectious Diseases, Boston Medical Center, 774 Albany St, Finland 5, Boston, MA 02118-2393. E-mail: spelton{at}bu.edu
Dr Pelton has research support from Wyeth and is a consultant to Shire Biologics.
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REFERENCES |
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- Kaplan SL, Mason EO Jr, Wald ER, et al. Decrease of Invasive pneumococcal infections in children among 8 children’s hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine.
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[Abstract/Free Full Text] - Progress toward eliminating Haemophilus influenzae type b disease among infants and children-United States, 1987–1997. MMWR Morb Mortal Wkly Rep. 1998;47:993–998
- From the Centers for Disease Control and Prevention. Updated recommendations on the use of pneumococcal conjugate vaccine in a setting of vaccine shortage-Advisory Committee on Immunization Practices.
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[Free Full Text] - Hausdorff WP, Siber G, Paradiso PR. Geographical differences in invasive pneumococcal disease rates and serotype frequency in young children. Lancet.2001; 357 :950 –952[CrossRef][Web of Science][Medline]
- Pneumococcal vaccines. WHO position paper. Wkly Epidemiol Rec. 1999;74:177–183. Available at: www.who.int/wer/pdf/1999/wer7423.pdf
PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics
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